Canny B J, O'Farrell K A, Clarke I J, Tilbrook A J
Department of Physiology, Monash University, Clayton, Victoria, 3168 Australia.
J Endocrinol. 1999 Aug;162(2):215-25. doi: 10.1677/joe.0.1620215.
There is a sex difference in the hypothalamo-pituitary-adrenal (HPA) axis of many species, although there are sparse data on the sheep. In the present study we have compared the HPA axes of intact and gonadectomised adult male and female sheep at the level of the median eminence, pituitary and adrenal glands using a variety of in vitro approaches. The concentration of arginine vasopressin (AVP) was higher (P<0.01) in the median eminence of male than female sheep, and was also elevated by gonadectomy of either sex (P<0.01). The concentration of corticotrophin-releasing factor (CRF) in the median eminence did not differ between the sexes, but was also elevated in both sexes following gonadectomy (P<0.01). Anterior pituitary pro-opiomelanocortin mRNA concentrations were higher (P<0.05) in intact male sheep than in intact females, with the levels in gonadectomised animals of both sexes being intermediate. In contrast to this finding, basal ACTH secretion from anterior pituitary cells was higher (P<0.05) in cultures derived from female sheep than those from males, but gonadectomy was without effect. There was no effect of sex or gonadectomy on in vitro ACTH secretion in response to AVP, CRF or the combination of AVP and CRF, and in all cases the combination of AVP and CRF generated greater (P<0.0001) ACTH secretion than AVP alone. AVP alone was more effective (P<0.01) than CRF alone as an ACTH secretagogue. The adrenal glands were larger (P<0.05) in female than male sheep, with no effect of gonadectomy. Basal cortisol production was greatest (P<0.05) in cultures of adrenal cells from intact male sheep, though ACTH- and 8BrcAMP-induced cortisol production was greater in the cultures of cells from females (P=0.05); there were no effects of gonadectomy. Cultures of adrenocortical cells from male sheep had greater (P<0.05) basal cAMP production, but ACTH-stimulated cAMP production did not differ between any of the groups of animals. These findings show a range of differences in the HPA axis of male and female sheep. Furthermore, they suggest that the heightened activity of the axis in the female occurs primarily due to differences at the level of the adrenal gland, and that greater adrenal responsiveness of female animals is due to differences in the latter stages of steroidogenesis, rather than an effect on ACTH signal transduction at its receptor.
许多物种的下丘脑 - 垂体 - 肾上腺（HPA）轴存在性别差异，不过关于绵羊的此类数据较少。在本研究中，我们采用多种体外实验方法，比较了成年雄性和雌性绵羊在完整状态以及性腺切除后的HPA轴，观察部位包括正中隆起、垂体和肾上腺。雄性绵羊正中隆起处的精氨酸加压素（AVP）浓度高于雌性（P<0.01），且无论雌雄，性腺切除后该浓度均升高（P<0.01）。正中隆起处促肾上腺皮质激素释放因子（CRF）的浓度在两性之间无差异，但性腺切除后两性的该浓度均升高（P<0.01）。完整雄性绵羊垂体前叶阿黑皮素原mRNA浓度高于完整雌性（P<0.05），两性性腺切除动物的该水平处于中间状态。与这一发现相反，雌性绵羊垂体前叶细胞的基础促肾上腺皮质激素（ACTH）分泌高于雄性（P<0.05），但性腺切除对此并无影响。性别和性腺切除对体外ACTH分泌对AVP、CRF或AVP与CRF组合的反应均无影响，并且在所有情况下，AVP与CRF组合产生的ACTH分泌均高于单独使用AVP（P<0.0001）。单独使用AVP作为ACTH促分泌剂比单独使用CRF更有效（P<0.01）。雌性绵羊的肾上腺比雄性大（P<0.05），性腺切除对此无影响。完整雄性绵羊肾上腺细胞培养物中的基础皮质醇产量最高（P<0.05），不过ACTH和8 - 溴环磷腺苷诱导的皮质醇产量在雌性细胞培养物中更高（P = 0.05）；性腺切除对此无影响。雄性绵羊肾上腺皮质细胞培养物的基础环磷腺苷（cAMP）产量更高（P<0.05），但ACTH刺激后的cAMP产量在任何一组动物之间均无差异。这些发现表明雄性和雌性绵羊的HPA轴存在一系列差异。此外，它们表明雌性中该轴活性增强主要是由于肾上腺水平的差异，并且雌性动物肾上腺反应性更高是由于类固醇生成后期的差异，而非对ACTH受体信号转导的影响。
